55828-88-1

Upstream product

• 24310-46-1 4-methoxyacetophenone phenylhydrazone 
• 105-58-8 Diethyl carbonate 
• 201230-82-2 carbon monoxide 
• 100-63-0 phenylhydrazine 
• 2196-99-8 2-chloro-1-(4-methoxyphenyl)ethanone 
• 59-88-1 phenylhydrazine hydrochloride 
• 2881-83-6 ethyl 4-methoxybenzoylacetate 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 22027-50-5 methyl 3-(4-methoxybenzoyl)acetate 

Downstream Products

• 1242100-50-0 1,4,5,6-tetrahydro-6-methyl-3-(4-methoxyphenyl)-1,6-diphenyl-pyrano[2,3-c]pyrazole 

Relevant academic research and scientific papers

Enantioselective Formal C(sp3)?H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives

Herein, we report the first enantioselective annulation of α-arylidene pyrazolones through a formal C(sp3)?H activation under mild conditions enabled by highly variable RhIII-Cpx catalysts. The method has a wide substrate scope and proceeds with good to excellent yields and enantioselectivities. Its synthetic utility was demonstrated by the late-stage functionalization of drugs and natural products as well as the preparation of enantioenriched [3]dendralenes. Preliminary biological investigations also identified the spiropyrazolones as a novel class of Hedgehog pathway inhibitors.

Structure-activity relationships of pyrazole-4-carbodithioates as antibacterials against methicillin–resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious hospital-acquired infections and is responsible for significant morbidity and mortality in residential care facilities. New agents against MRSA are needed to combat rising resistance to current antibiotics. We recently reported 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) as a new bacteriostatic agent against MRSA that appears to act via a novel mechanism. Here, twenty nine analogs of HMPC were synthesized, their anti-MRSA structure-activity relationships evaluated and selectivity versus human HKC-8 cells determined. Minimum inhibitory concentrations (MIC) ranged from 0.5 to 64 μg/mL and up to 16-fold selectivity was achieved. The 4-carbodithioate function was found to be essential for activity but non-specific reactivity was ruled out as a contributor to antibacterial action. The study supports further work aimed at elucidating the molecular targets of this interesting new class of anti-MRSA agents.

Asymmetric [3 + 3] Annulation of Copper-Allenylidenes with Pyrazolones: Synthesis of Chiral 1,4-Dihydropyrano[2,3- c]pyrazoles

The copper-catalyzed asymmetric [3 + 3] annulation of ethynyl benzoxazinanones with pyrazolones has been achieved, providing simple access to 1,4-dihydropyrano[2,3-c]pyrazole derivatives in moderate to excellent yields with excellent enantioselectivities (up to 99% ee). Compared with previous annulation reactions of copper-allenylidenes from ethynyl benzoxazinanones, the current reaction fused the three carbon atoms of the propargyl moiety into a heterocyclic framework.

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approach has to consider the solid form of the materials and compatibility of any auxiliary used. This has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields.

Design, synthesis and anticancer activity of some novel 5-(4-methoxyphenyl)-2,4-dihydro-3H-pyrazol-3-one derivatives

New pyrazole derivatives were designed and synthesized by the reaction of 5-(4-methoxyphenyl)-2,4-dihydro-3H-pyrazol-3-one (4) or 5-(4-methoxyphenyl)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (5) with series of aldehydes, substituted amines, isatins and phenylisothiocynate to yield 6a-j, 7a-k, 9a-d and 10a-b, respectively. The synthesized compounds were examined in vitro for their anti-tumor activities against HepG-2, PC-3 and HCT-116 human carcinoma cell lines using MTT assay. Eight compounds showed good anticancer activities against HCT-116 carcinoma cells and five compounds showed good anticancer activities against PC-3 cancer cells but all the compounds showed weak or no anticancer activities against HepG-2 liver cancer.

Synthesis of Spiropentadiene Pyrazolones by Rh(III)-Catalyzed Formal sp3 C-H Activation/Annulation

A Rh-catalyzed enol-directed formal sp3 C-H activation/annulation of α-arylidene pyrazolones with alkynes has been developed. This reaction provides a convenient route to synthesize spiropentadiene pyrazolones in good to excellent yields at room temperature, exhibiting good functional group tolerance, gram scalability, and high regioselectivity. Of note, the α-arylidene pyrazolone was introduced as a novel C3 synthon in C-H activation/annulation.

Anti-cancer compounds targeting Ral GTPases and methods of using the same

The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

ANTI-CANCER COMPOUNDS TARGET RAL GTPASES AND METHODS OF USING THE SAME

Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Synthesis of novel Ral inhibitors: An in vitro and in vivo study

Chemical synthesis was performed to produce a series of 6-amino-1,3-disubstituted-4-phenyl-1,4-dihydro pyrano[2,3-c]pyrazole-5-carbonitrile compounds (14–57) which were characterized by1H NMR,13C NMR and LC/MS–MS. These compounds were assessed for their effect on the in vitro anchorage independent growth of human lung cancer cell line H2122 and IC50values calculated. Two of the more potent compounds, BQU057 40 and BQU082 57 also displayed a dose dependent effect on RalA and RalB activity in H2122 spheroids using the common RalBP1 pull-down assay. Mouse PK and tissue distribution studies on 40 and 57 were performed and demonstrated that parent drug was present in tumor 3.0 h post ip (50 mg/Kg) dose.

POLYCYCLIC DERIVATIVES TARGETING RAL GTPASES AND THEIR THERAPEUTICAL APPLICATIONS

Contemplated compounds, compositions and methods are directed to Ral GTPase inhibitors with improved activity.